This proposal requests support for years 26-30 for the Environmental Pathology/Toxicology Program (EP/T) at the University of Washington, which has been funded by NIEHS since 1978. The goals of the Program are to offer training to predoctoral students and postdoctoral fellows in research on cell and molecular mechanisms of environmental disease and on mechanism-based risk assessment. The Program is a collaborative effort of faculty in the Department of Pathology (School of Medicine) and the Department of Environmental Health (School of Public Health and Community Medicine). To replace faculty who have retired or left the University and provide additional strengths to their offerings, the investigators propose to add eight new core faculty, including three well-known investigators in the area of biotransformation from the School of Pharmacy. The Program will have 22 core faculty grouped into research area clusters established in 1998: Biotransformation and Oxidative Injury, to be renamed Biotransformation and Xenobiotics (Dr. David Eaton, leader); Neuro- and Developmental Toxicology (Dr. Lucio Costa, leader); Mechanistic Approaches to Risk Assessment (Dr. Elaine Faustman, leader), and Mutagenesis and Molecular Carcinogenesis (Dr. Raymond Monnat Jr., leader). The EP/T Program is directed by Dr. Nelson Fausto (Program Director), Dr. Elaine Faustman (Deputy Director), and a Steering Committee constituted by the leaders of the research clusters. The EP/T Program is closely associated with four NIEHS supported Centers at the University of Washington, which focus on Ecogenetics, Toxicogenomics, Mouse Genomics and Biomarkers as well as Centers specialized in risk analysis. The Program supports 8 predoctoral and 3 postdoctoral students. Given the excellent record of training and productivity of the faculty, the interactive and interdisciplinary nature of their activities, and the outstanding environment for research in environmental health at the University of Washington, the investigators propose to increase the number of trainees supported by the EP/T Program to 9 predoctoral students and 4 postdoctoral fellows.